Master of Architecture / Department of Architecture / Matthew Knox / The purpose of this study is to examine how the industrial process of rapid prototyping might reshape practice and making in architecture. Rapid prototyping is defined as an accelerated, adaptive evolution of a system or its components in some form using computer-aided drafting and manufacturing. Historically, all architecture was the intelligence of a single maker—the master builder. Specialization has caused architecture to fragment with architects serving only as designers. This report explores the ability of computer-aided drafting and manufacturing technologies to streamline the design procedure, which potentially increases the architect’s input into the process of building. Effectually, the architect narrows the distance between the design and the built—returning the architect to the role of master builder. An actual design exercise will examine the connection of architectural practice to making. To apply this research a habitable space was constructed through the incorporation of rapid prototyping.

Objectives: This thesis included 6 manuscripts which focused on the analysis of adverse events following immunization (AEFIs), including general health services utilization (emergency room (ER) visits and hospital admissions) and specific diagnoses (e.g. febrile convulsions). The main objectives of this research were: 1) To demonstrate the utility of the self-controlled case series (SCCS) design coupled with health administrative data for studying the safety of vaccines; 2) Introducing an innovative approach using relative incidence ratios (RIRs) within an SCCS analysis to identify risk factors for AEFIs and to overcome the healthy vaccinee bias; and 3) To demonstrate how SCCS and RIR analyses of health services outcomes in health administrative data can provide important insights into underlying physiological and behavioural mechanisms. Data Sources: This work utilized Ontario health administrative data housed at the Institute for Clinical Evaluative Sciences (ICES). The study included all children born in Ontario, Canada between 2002 and 2011 (over 1 million children). Vaccinations were identified using OHIP fee for service billing codes for general vaccination. Admissions and ER visits for any reason were identified in the Discharge Abstract Database (DAD) and National Ambulatory Care Reporting System (NACRS). Primary reasons for admissions and ER visits were investigated using ICD-10-CA codes reported in the DAD and NACRS databases. Statistical Methods: The self-controlled case series design (SCCS) was used to calculate the relative incidence of admissions, ER visits and other AEFIs. To investigate relative incidence for AEFIs across risk groups of interest, as well as addressing the healthy vaccinee effect bias, RIRs were calculated. RIRs are the ratio of incidence ratios in a subgroup of interest relative to a designated reference group. Results and Conclusions: The combined approach of using the SCCS design and RIRs to identify risk factors and overcome the healthy vaccinee bias proved to be a powerful approach to studying vaccine safety. Future work will be important to characterize the performance and validity of the SCCS + RIR approach in the presence of increasing levels of confounding and differing manifestations of the healthy vaccinee bias, as well as to elucidate the biological and behavioural mechanisms underlying our findings.

Background: With usual supplementation practices, most children are Vitamin D Deficient (VDD) following Congenital Heart Disease (CHD) surgery and alternative regimens need consideration. Methods/Results: i) A systematic review identified 88 pediatric trials of high dose vitamin D. Studies evaluating the Institute of Medicine (IOM) Tolerable Upper Intake Level (UL) did not rapidly normalize levels, while loading therapy (≥ 40000 IU) did so within 3 days. Hypercalcemia occurred more often with doses above 400000 IU. ii) A double blind RCT was designed to determine whether pre-operative administration of the IOM UL can prevent post-operative VDD. Results after the first 30 participants completed study procedures demonstrated it was possible to recruit (1.8 patients per month) and complete study procedures (i.e. blood collection). Unfortunately few participants (45%) received more than 30 doses of study drug. Conclusion: Prevention of post-operative VDD in the majority of CHD patients will require alternatives to the IOM recommendations.

Background: In September 2005, scientific journals began requiring trial protocol registration to increase transparency and accountability. Objective: My primary objectives were: develop a database of linked protocols and publications for surgical randomized control trials (RCTs); estimate the proportion published; and determine the proportion exhibiting selective outcome reporting. Methods: A systematic search of the clinicaltrials.gov database was conducted identifying surgical RCTs, completed between 2006 and 2012. Protocols were linked with publications. Primary outcomes were compared. Results: We identified a cohort of 743 surgical RCT protocols. The proportion of registered trials which published their primary results was 0.49 (n=364). The proportion of selective outcome reporting was estimated to be 0.244, significantly lower than the previous estimate (p<0.001). Conclusion: More than half of the completed surgical RCTs were unpublished, and one quarter of those published selectively reported their primary outcome. This supports the notion that significant bias is present in the surgical literature.

Class of 2008 Abstract / Objectives: 1) To determine if data on weight change in the placebo arm of RCT's for weight loss were available, and 2) to conduct a pilot meta-analysis to estimate the average weight change in the placebo arm. Methods: Four randomized placebo controlled trials of rimonabant for weight loss were retrieved. A draft data extraction form was developed to record weight loss and demographic data. Potential for bias was assessed on design issues related to withdrawals, blinding, allocation procedure, adherence, and manufacturer influence. Based on available data, a forest plot was constructed and heterogeneity was assessed. The a priori alpha level was 0.05. Results: The placebo groups from all studies were similar. The pooled data indicated that individuals in the placebo arm lost an average of 3.3 kg, p < 0.001. One study had a significantly greater completion rate than the other studies. Participants were prescribed a hypocaloric diet and were instructed to increase physical activity but no data were reported on calories consumed or amount of physical activity. Weight loss of 5% ranged from 15-20% of participants. There was potential for bias relating to reported adherence, allocation concealment process, and manufacturer funding. Conclusions: Participants in the placebo arm of rimonabant trials lost an average of 3.3 kg, which was statistically significant. Little can be learned about weight loss in the placebo arm because no data on calories consumed, amount of exercise, or hunger were reported. Information from other RCT's is needed to provide additional data and to confirm the findings.

The effect of peptide charge on the self-assembly and gelation behaviour of three octa-peptides: VEVKVEVK (VEK2), VKVKVEVK (VEK3) and VEVEVKVE (VEK1) has been investigated and characterised. The critical gelation concentration of each peptide was found to correlate with the charge modulus carried by the peptide and to be independent of the sign of the charge. Hydrogels formed were found to be transparent and stable when the peptide charge modulus is > 1. No differences in hydrogel structure or mechanical properties, as probed by TEM and SAXS and shear rheology, were found when the peptides were at the same concentration and carried the same charge modulus. These peptides were shown to form dense fibrillar network formed by β-sheet rich single fibre which lateral aggregation is controlled by the peptide charge modulus. The increase in fibre lateral aggregation with decreasing charge modulus was found to correlate with the increase in hydrogel mechanical properties, showing that fibre lateral aggregation pays a key role in controlling the mechanical properties of these hydrogels. The release profiles from VEK1 and VEK3 at pH 7 of two hydrophilic model drug molecules, namely napthol yellow (NY) and martius yellow (MY) was analysed using UV-Vis spectrophotometry. The incorporation of the guest molecules did not affect the self-assembly of the peptide at a molecular level but did affect the level of lateral fibre aggregation observed and therefore the mechanical properties of the hydrogels. The release of each of the model compounds was monitored over time and shown to be controlled by Fickian diffusion. The guest molecule diffusion rate D was dependent on the ratio between the overall effective charges carried by the peptide, i.e.: the fibrillar network, and the overall charges carried by the guest molecules but independent from the hydrogel concentration and mechanical properties, in the concentration and guest loading range investigated. This work shows that the rate of release of small drug molecules can be manipulated, not only by changing the charges on the guest molecules, but also by manipulating the charged state of the self-assembling peptide molecule and through it the charge state of the fribrillar network. Furthermore the VEK3 system was conjugated to a series of thermo-responsive synthetic polymers which imparted a significant change in mechanical properties, assembled structures and release profiles upon heating. Observed changes when above the polymers LCST include increased mechanical strength, fibre thickening and increased diffusion coeffcients. The synthesis, and subsequent characterisation, of these materials is the first time responsive hydrogels of OEGMA copolymers has been reported.

The Z-pinches in a vacuum spark can be classified into slow, fast and superfast according to their pinch durations. Their emission characteristics are investigated in the visible, ultraviolet and the X-ray wavelengths. The plasma during a fast pinch was found to have an electron temperature between 100 and 600eV. The superfast pinch resulted in a minute cylindrical plasma approximately 40 μm in diameter, with an electron temperature of 1 to 4keV and a lifetime of less than 4ns. The slow and the fast pinch were found to be in agreement with the theoretical results predicted by a shock wave model. The formation of the superfast pinch and its associated high density and temperature were explained as the results of magnetohydrodynamic instability. / Science, Faculty of / Physics and Astronomy, Department of / Graduate

archives@tulane.edu / 1 / Olakunle Francis Ojo

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第21705号 / 人健博第71号 / 新制||人健||5(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 市橋 則明, 教授 黒木 裕士, 教授 妻木 範行 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

Repellents play a key role in preventing mosquito-borne diseases such as malaria by reducing human-vector contact. The general mechanism of action relies on providing a repelling vapour around the applied area on the skin. Thus, the proper evaporation rate and consistency of the composition of the released vapour are factors determining the performance of repellent formulations. The formulation should evaporate fast enough to provide a sufficient level of repellence during its life time. However, if evaporation proceeds too fast, then it will be depleted rapidly so that activity is lost within a short period of time, which makes the repellent inefficient. Several controlled-release approaches have been developed to improve both the protection time and level. However, these techniques have inherent drawbacks from the industrial point of view. Moreover, these techniques mostly focus only on reducing the release rate, while the consistency of the vapour composition has not been addressed. In the present study, a novel approach towards controlling the evaporation behaviour of repellents is proposed. It is based on engineering the molecular interactions in order to design negative pseudo-azeotrope formulations. Negative pseudo-azeotrope mixtures are less volatile than the pure parent components and they do not undergo separation during evaporation. The feasibility of the idea was investigated by studying the molecular structure of generally available repellents. Among known molecular interactions, hydrogen bonding has the most likely impact on the formation of azeotropes and in particular pseudo-azeotropes. Thus, established repellents were classified based on their chemical structures and their capability to take part in hydrogen bonding. Next, a simple spectroscopic method for anticipating pseudoazeotropes formation was developed. Binary compositions of nonanoic acid and ethyl butylacetylaminopropionate (IR3535) showed a potential for forming pseudo-azeotrope mixtures. Hence R3535 and nonanoic acid were selected as model compounds to test the hypothesis. An experimental technique to confirm pseudo-azeotrope formation and to locate the composition of the probable pseudo-azeotrope point was required. To this end, an oven test was designed. The temporal mass loss, under an isothermal program, of a series of evaporating mixtures was measured. Simultaneously, the Fourier transform infrared (FTIR) spectra of the liquid remaining was recorded. Inverse analysis techniques were used to determine the composition of remaining liquid mixtures from the recorded FTIR spectra. The oven tests revealed that, as vaporisation progressed, the composition of the liquid remaining and the emitted vapour converged to a fixed IR3535 content of ca. 75 mol%. Mixtures close to this composition also featured the lowest volatility. Oven test also showed that the composition of the liquid mixtures diverged from the fixed IR3535 content of ca. 10 mol%. Mixtures close to this composition featured the highest volatility. These observations showed that IR3535 and nonanoic acid forms two pseudo-azeotrope compositions, i.e. a negative pseudo-azeotrope at an IR3535 content of ca. 75 mol%, and a positive pseudo-azeotrope at IR3535 content of ca. 10 mol%. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were applied to check these results. TGA confirmed that the negative pseudo-azeotrope mixture is less volatile while the positive pseudo-azeotrope is more volatile than the parent compounds. The DSC results revealed that in comparison with the pure compounds, negative pseudo-azeotrope had a lower boiling point onset while the positive pseudo-azeotrope had a higher boiling point. Although negative pseudo-azeotrope repellent formulations have the desired lower constant release rate, their repellent activity needed to be tested. This is due to the fact that mixing the ingredients to formulate a negative pseudo-azeotrope results in interactions among the components. As a consequence, the inherent repellence effect of the compounds might have been impaired in the mixture. The modified arm-in-cage test was used to test the repellence of the controlled-release repellent formulation i.e. the negative pseudo-azeotrope of the IR3535 + nonanoic acid system. Results showed that the mixture featured improved performance with respect to both repellence efficacy and persistence. Moreover, the negative pseudo-azeotrope also exhibited a knock down effect, even resulting in mortality of most of the test mosquitoes. The presence of two pseudo-azeotrope points at different composition in the IR3535 + nonanoic acid system is a rare occurrence, analogous to double azeotropy. Thus, molecular simulation techniques were used to explore the nature of system and the interactions responsible for this unique behaviour. Gibbs-Monte Carlo simulation results suggest that variations in the sizes of the molecular clusters present in the liquid at various compositions might be responsible. They revealed that IR3535 and nonanoic acid in neat form are both highly structured liquids. The break-down in the structure of IR3535 at high concentrations of the acid may be the origin of increased evaporation rate and formation of the positive pseudo-azeotrope. On the other hand, negative pseudo-azeotrope may be resulted from formation of bulkier clusters at the ration of 3:1 (IR3535: nonanoic acid). / Thesis (PhD (Chemical Technology))--University of Pretoria, 2016. / English / PhD (Chemical Technology) / Unrestricted